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EZH2 is an enzyme that silences genes. The first drug against it treated a rare sarcoma and some lymphomas until it was withdrawn in 2026 for causing second blood cancers. This dossier gathers the 3 products (0 approved), 13 trials, 8 pathways and 1 resistance route in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Catalytic subunit of PRC2, writes H3K27me3.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | >90% | INI1 (SMARCB1) loss in epithelioid sarcoma (EZH2 dependency) | Tazemetostat withdrawn March 2026 | FDA |
| Diffuse large B-cell lymphoma | 20-25% | EZH2 Y641 mutation in follicular/GCB lymphoma | Tazemetostat withdrawn March 2026 | Wikipedia |
| Prostate cancer | n/a | Overexpression in CRPC; no threshold | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Phase 3 | Phase 2 | Withdrawn or failed |
|---|---|---|---|
| Small molecule 3 |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Recruiting | A Randomized, Double-blind, Multicenter Phase III Study of XNW5004 Tablets in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma | - | ||
| 3 | Active | Symphony-1: A Phase 1b/3 Double-Blind, Randomized, Active-Controlled, 3-Stage, Biomarker Adaptive Study Of Tazemetostat Or Placebo In Combination With Lenalidomide Plus Rituximab In Subjects With Relapsed/Refractory Follicular Lymphoma | - | ||
| 3 | Recruiting | A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF PF-06821497 (MEVROMETOSTAT) WITH ENZALUTAMIDE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MEVPRO-2) | - | ||
MEVPRO-1 NCT06551324 | 3 | Active | mCRPC after abiraterone: mevrometostat + enzalutamide vs physician's choice (enzalutamide or docetaxel) | - | |
| 3 | Recruiting | A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF MEVROMETOSTAT (PF-06821497) WITH ENZALUTAMIDE IN METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MEVPRO-3) | - | ||
NCI-COG Pediatric MATCH (APEC1621) NCT03155620 | platform | Active | Relapsed or refractory solid tumours, non-Hodgkin lymphomas and histiocytic disorders, age 1-21: tumour sequencing then assignment to one of a dozen single-agent targeted-therapy phase 2 arms | Actionable alteration in 31.5% of the first 1,000 tumours; 28.4% assigned and 13.1% enrolled on a treatment arm. | |
| 2 | Completed | NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of Tazemetostat in Patients With Tumors Harboring Alterations in EZH2 or Members of the SWI/SNF Complex | - | ||
| 2 | Recruiting | Phase II Study of XNW5004 in the Treatment of Patients With Relapsed or Refractory Follicular Lymphoma (EZH2 Wild-type) | - | ||
| 1/2 | Recruiting | A Multicenter, Open-label, Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of SHR-4394 in Combination With Anti-tumor Therapy in Participants With Prostate Cancer | - | ||
| 1/2 | Recruiting | An Exploratory Phase 1b/2a Multicenter, Open-Label, Novel-Novel Combination Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CC-92480 (BMS-986348) in Novel Therapeutic Combinations in Participants With Relapsed or Refractory Multiple Myeloma | - | ||
| 1/2 | Recruiting | A Phase Ib/II Clinical Study of XNW5004 Combined With CHOP/CHOEP in the Treatment of Untreated Peripheral T-Cell Lymphoma | - | ||
| 1/2 | Recruiting | A Phase Ib/II Study of XNW5004 Tablet in Combination With Enzalutamide in Subjects With Metastatic Castration-resistant Prostate Cancer (mCRPC) Who Failed Prior Novel Hormone Therapy | - | ||
| 1 | Withdrawn | Previously untreated advanced epithelioid sarcoma with loss of INI1/SMARCB1: tazemetostat added to doxorubicin, the safety run-in of the planned randomised confirmatory trial; started December 2019, 25 enrolled, terminated by the sponsor | - |
Schlafen-11 is required for replication-stress-induced death; its epigenetic silencing confers resistance to TOP1 (and platinum) agents.
Some cancer cells behave like stem cells: they can regrow the whole tumour, resist treatment, and switch identities. This plasticity explains why tumours come back and why some lung and prostate cancers transform into a different cancer type under therapy.
Which nodes have drugs →Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.
Which nodes have drugs →Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation: they go quiet, stop dividing, and wait. These persisters are the seed of relapse. They are hard to kill precisely because they are not doing much, but they have their own weaknesses.
Which nodes have drugs →Cancer changes not just its genes but how they are read: chemical tags on DNA and histones silence guardians and awaken growth programmes. Unlike mutations, these changes are reversible, which is the hope behind epigenetic drugs.
Which nodes have drugs →Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.
Which nodes have drugs →This KEGG map collects the small RNA molecules (microRNAs) that are switched up or down in nine common cancers and shows which oncogenes and tumour suppressors they silence. It matters because a single microRNA can dial down dozens of genes at once, so losing or gaining one reshapes whole signalling routes.
Which nodes have drugs →A machine that opens and closes DNA so genes can be read. One in five cancers has a broken part (ARID1A, SMARCA4, PBRM1), and losing one part often creates a dependence on its twin, which is the basis for new synthetic-lethal drugs.
Which nodes have drugs →To make a good antibody, a B cell has to deliberately damage its own DNA and keep dividing while it does. The germinal centre is where that happens, under strict time limits. Most B-cell lymphomas are cells that went through it and did not come out.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"EZH2" OR ABSTRACT:"EZH2" OR TITLE:"PRC2" OR ABSTRACT:"PRC2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about EZH2, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/ezh2.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/ezh2.json. Licence CC BY-NC 4.0.